7 results on '"Bohley, Marilena"'
Search Results
2. Photopolymerization Inks for 3D Printing of Elastic, Strong, and Biodegradable Oral Delivery Devices.
- Author
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Yuts, Yulia, Bohley, Marilena, Krivitsky, Adva, Bao, Yinyin, Luo, Zhi, and Leroux, Jean‐Christophe
- Subjects
- *
THREE-dimensional printing , *DRUG delivery devices , *PHOTOPOLYMERIZATION , *DRUG delivery systems , *PRINTING ink - Abstract
Three‐dimensional (3D) printing via vat photopolymerization is transforming the manufacturing paradigms of biomedical devices, offering tremendous advantages for the production of customized advanced drug delivery systems. However, the existing commercial inks often lack the ability to simultaneously provide elasticity, strength, and biodegradability. Herein, photopolymerizable inks based on poly(β‐aminoester) diacrylates and N‐vinyl pyrrolidone are used to address these limitations. These biodegradable polymers enable the digital light processing 3D printing of elastomers with adjustable elongation at break (103–762%), stress at failure (0.2–8.3 MPa), and hydrolysis rates ranging from 25 min to 80 days. The authors are able to synthesize a soft polymer that possess properties akin to natural latex, which can enhance its elastic modulus when subjected to high strains. It can withstand 762% stretch with a maximum strength of 8.3 MPa. In addition, this polymer demonstrates cytocompatibility and unique biodegradation properties under simulated gastrointestinal conditions (within hours at pH 6.8). By utilizing this elastomer, a prototype of an expandable oral drug delivery device that has the ability to degrade within the average transit time in the jejunum is manufactured. This study paves the way to leverage vat photopolymerization 3D printing in the creation of complex prototypes of biomedical devices where strength, elasticity and biodegradability are essential. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Targeted drug delivery to the retinal pigment epithelium: Untapped therapeutic potential for retinal diseases.
- Author
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Bohley, Marilena, Dillinger, Andrea E., Tamm, Ernst R., and Goepferich, Achim
- Subjects
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RETINAL diseases , *TARGETED drug delivery , *RHODOPSIN , *MACULAR degeneration , *DIABETIC retinopathy , *EPITHELIUM - Abstract
• Most retinal diseases underly multifactorial pathomechanisms. • The retinal pigment epithelium (RPE) plays a key part in these pathomechanisms. • Targeted RPE therapy can be used to efficiently treat retinal diseases. • Intravitreal and systemic nanoparticle systems can reach the RPE. • Guidance for the development of RPE-specific nanotherapeutics is provided. The retinal pigment epithelium (RPE) plays a crucial part in sight-threatening diseases. In this review, we shed light on the pivotal implication of the RPE in age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity; and explain why a paradigm shift toward targeted RPE therapy is needed to efficiently fight these retinal diseases. We provide guidance for the development of RPE-specific nanotherapeutics by giving a comprehensive overview of the possibilities and challenges of drug delivery to the RPE and highlight successful nanotherapeutic approaches targeting the RPE. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Intracellular availability of poorly soluble drugs from lipid nanocapsules.
- Author
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Bohley, Marilena, Haunberger, Alexandra, and Goepferich, Achim M.
- Subjects
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VASCULAR endothelial growth factors , *DRUG carriers - Abstract
Lipid nanocapsules (LNCs) are extensively used as drug carrier systems, due to their small size distribution, biocompatibility and ease of preparation. They are especially useful for lipophilic drugs to overcome physicochemical constraints that limit their efficacy, such as low solubility in aqueous media. The aim of this work was to investigate the relationship between the intracellular availability of poorly soluble drugs delivered via LNCs and their biological efficacy in cells in vitro. Cyclosporin A (CsA) with a logP Oct = 4.3 (Lucangioli et al., 2003) and Itraconazole (It) with a logP Oct = 6.2 (Bhardwaj et al., 2013) served as model lipophilic compounds, as they are highly promising candidates for the treatment of neovascular ocular diseases. Due to their lipophilic properties and the resulting preference for the oily core of LNCs, high encapsulation efficiencies were achieved. Drug-loaded LNCs with particle sizes around 50 nm were grafted with an αvβ3 integrin ligand (RGD) to optimize cellular uptake by human dermal microvascular endothelial cells. Even though RGD-LNCs showed excellent internalization, they exhibited insufficient inhibitory effects in vitro regarding endothelial cell proliferation, vascular endothelial growth factor expression, and tube formation in contrast to free drugs. This loss of efficacy could be explained by negligible intracellular availability of the poorly soluble drugs from LNCs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
5. Design of dye and superparamagnetic iron oxide nanoparticle loaded lipid nanocapsules with dual detectability in vitro and in vivo.
- Author
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Bohley, Marilena S., Birch, Emily, Baumann, Felix J., Dillinger, Andrea E., Tamm, Ernst R., and Goepferich, Achim M.
- Subjects
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NANOCAPSULES , *INDUCTIVELY coupled plasma atomic emission spectrometry , *FERRIC oxide , *IRON oxide nanoparticles , *IRON oxides - Abstract
Lipid nanocapsules are treasured nanoparticulate systems, although they lack detectability in biological environments. To overcome this, we designed LNCs loaded simultaneously with fluorescent dye and superparamagnetic iron oxide nanoparticles (Dual LNCs). The introduction of both labels did not alter nanoparticle characteristics such as size (50 nm), size distribution (polydispersity index < 0.1) or surface modifications, including the effectiveness of targeting ligands. Furthermore, the colloidal stability, particle integrity and biocompatibility of the nanoparticles were not negatively affected by label incorporation. These Dual LNCs are concomitantly visualizable via fluorescence and transmitted light imaging after either the internalization by cells or systemic administration to mice. Importantly, they are detectable in liver sections of mice using transmission electron microscopy without additional enhancement. The iron content of 0.24% (m/m) is sufficiently high for precise quantification of nanoparticle concentrations via inductively coupled plasma optical emission spectroscopy. Dual LNCs are precious tools for the investigation of in vitro and in vivo performances of lipid nanocapsule formulations, since they allow for the use of complementary imaging methods for broad range detectability. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
6. Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?
- Author
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Bohley M and Leroux JC
- Abstract
Oral peptide delivery is trending again. Among the possible reasons are the recent approvals of two oral peptide formulations, which represent a huge stride in the field. For the first time, gastrointestinal (GI) permeation enhancers (PEs) are leveraged to overcome the main limitation of oral peptide delivery-low permeability through the intestinal epithelium. Despite some success, the application of current PEs, such as salcaprozate sodium (SNAC), sodium caprylate (C8), and sodium caprate (C10), is generally resulting in relatively low oral bioavailabilities (BAs)-even for carefully selected therapeutics. With several hundred peptide-based drugs presently in the pipeline, there is a huge unmet need for more effective PEs. Aiming to provide useful insights for the development of novel PEs, this review summarizes the biological hurdles to oral peptide delivery with special emphasis on the epithelial barrier. It describes the concepts and action modes of PEs and mentions possible new targets. It further states the benchmark that is set by current PEs, while critically assessing and evaluating emerging PEs regarding translatability, safety, and efficacy. Additionally, examples of novel PEs under preclinical and clinical evaluation and future directions are discussed., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
7. A single intravenous injection of cyclosporin A-loaded lipid nanocapsules prevents retinopathy of prematurity.
- Author
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Bohley M, Dillinger AE, Schweda F, Ohlmann A, Braunger BM, Tamm ER, and Goepferich A
- Subjects
- Animals, Cyclosporine pharmacology, Cyclosporine therapeutic use, Humans, Infant, Newborn, Inflammation drug therapy, Injections, Intravenous, Lipids, Mice, Vascular Endothelial Growth Factor A, Nanocapsules therapeutic use, Retinopathy of Prematurity drug therapy, Retinopathy of Prematurity prevention & control
- Abstract
Retinopathy of prematurity (ROP) is a retinal disease that threatens the vision of prematurely born infants. Severe visual impairment up to complete blindness is caused by neovascularization and inflammation, progressively destroying the immature retina. ROP primarily affects newborns in middle- and low-income countries with limited access to current standard treatments such as intraocular drug injections and laser- or cryotherapy. To overcome these limitations, we developed a nanotherapeutic that effectively prevents ROP development with one simple intravenous injection. Its lipid nanocapsules transport the antiangiogenic and anti-inflammatory cyclosporin A efficiently into disease-driving retinal pigment epithelium cells. In a mouse model of ROP, a single intravenous injection of the nanotherapeutic prevented ROP and led to normal retinal development by counteracting neovascularization and inflammation. This nanotherapeutic approach has the potential to bring about a change of paradigm in ROP therapy and prevent millions of preterm born infants from developing ROP.
- Published
- 2022
- Full Text
- View/download PDF
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